title: Generation, characterization and therapeutic potential of anti-feline TNF-alpha MAbs for feline infectious peritonitis.
abstract: Feline infectious peritonitis (FIP) is a lethal infectious disease affecting domestic and wild cats. Several reports suggested that TNF-alpha is related to the progression of FIP. Thus, the administration of a feline TNF-alpha-neutralizing antibody to cats with FIP may reduce the disease progression. In this study, we have prepared nine monoclonal antibodies (MAbs) that recognize feline TNF-alpha. All MAbs neutralized recombinant TNF-alpha. The 50% inhibitory concentrations (IC50) of the MAbs for the cytotoxicity of recombinant TNF-alpha were 5-684 ng/ml. MAb 2-4 exhibited high neutralizing activity against natural TNF-alpha derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-alpha-induced conditions in vitro: (i) an increase in the survival rate of neutrophils from cats with FIP, (ii) aminopeptidase N (APN) mRNA expression in macrophages, and (iii) apoptosis of a feline T-lymphocyte cell line.
authors.affiliation: Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan. Electronic address: dv12003f@st.kitasato-u.ac.jp.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Doki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Takano
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Michiyo
authors.initials: M
authors.lastname: Nakamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hohdatsu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology; D002415:Cats; D016765:Coronavirus, Feline / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D016766:Feline Infectious Peritonitis / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Feline coronavirus; Feline infectious peritonitis; Tumor necrosis factor-alpha